Life expectancy is approximately 20 years shorter in schizophrenia and 10 years shorter in mood disorder with psychosis than in the general population, which is almost entirely due to natural-cause mortality. One proposed explanation is that psychotic disorders are associated with accelerated aging. Substantial evidence indicates that this population experiences premature declines in three functional domains: internal (i.e., age- related medical disorders), cognitive, and physical. However, it is unknown whether these declines are explainable by exposure to risk factors highly elevated in psychotic disorders (obesity, poverty, smoking, low physical activity, poor diet, inadequate medical care, etc) or are also due to pathophysiology of psychosis itself. Indeed, biological processes associated with psychosis?genetic, neural (P3 and mismatch negativity), and allostatic load (metabolic problems, increased inflammation, hypothalamic-pituitary-adrenal axis dysregulation, and hypertension)?were found to predict accelerated aging in the general population, but this has not been tested in psychotic disorders. Moreover, it remains uncertain when accelerated aging starts and how rapidly it progresses, as prior studies typically began with older patients. Prevention of premature aging in psychotic disorders would extend life and improve health of millions of people, but it is unclear how to target such efforts, because fundamental information is lacking on trajectories of aging and their determinants in psychosis. The Suffolk County Mental Health Project (SCMHP; MH094398) offers a unique opportunity to fill these crucial gaps. It is the only US epidemiologic study designed to examine health, cognition, and physical performance in psychotic disorders over 27 years following first admission (from mean age 30 to 57). In addition, the study has gathered a wealth of information on premorbid risk factors. It also includes a geographically and demographically matched never-psychotic comparison group. Thorough assessments of cases were done 6 times during the first two decades. At Year 20 (mean age 49), both case (N=385) and never-psychotic (N=261) groups completed a comprehensive psychiatric evaluation, medical history, physical performance tests, anthropometric exam, cognitive testing, event-related potentials battery, assays of blood samples, and genotyping. The present proposal is to reassess cases and never-psychotic participants at ages 54 and 57 to trace divergence of aging trajectories during a pivotal period (age 49 to 57, when medical morbidity is expected to double and cognitive and physical functioning begin to decline) and identify risk factors and biological vulnerabilities that help to determine what path aging takes. This innovative design will enable us to clarify when and why aging is accelerated in psychotic disorders, and where interventions can be applied most productively to extend life expectancy and health of this population.